This broadly titled project has over the years covered all my major research interests and represented by only source of research support. Although the individual problems that have been tackled as part of this project have included many and varied systems and techniques, I still feel that it represents a coherent and logical approach toward a broader and more detailed understanding of the unifying principles involved in correlating structure and function of proteins. According to my current understanding of this field, I judge the following three areas to be the most important ones for me to pursue at this time: I. Elucidation of the structural and functional coupling of subunits in multimeric proteins, II. The correlation of solid state structural information with solution properties of proteins and the elucidation of the dynamic structural changes that are associated with biological function, and III. The elucidation of the role of the oligosaccharide components in determining the biological properties of glycoproteins. These are the three major research proposals, to be tackled primarily by classical methods of solution chemistry such as chemical modification with bifunctional and monofunctional reagents, accompanied by careful characterization of the broadest possible spectrum of structural and functional parameters. Along with the 3 central areas, I also hope to explore the possible application of chemical modification techniques to the stabilization and protection of enzymes to give derivatives which may be used in enzyme replacement treatment of genetic diseases.